Improvement of HIV-Specific Immunity in HIV-Infected Twins Treated with Highly Active Antiretroviral Therapy, Interleukin 2, and Syngeneic Adoptively Transferred Cells

Tsoukas, Christos; Turner, Howard M.; Hatzakis, George; G, Blake; Goodhew, John E; Kilby, Donald; Kovacs, Colin; Luetkehoelter, Jonathan; Routy, Jean‐Pierre; Walmsley, Sharon; Bernard, Nicole F.

doi:10.1089/088922201750290014

Cited by 7 publications

(5 citation statements)

References 55 publications

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“…Tsoukas et al, gave to five HIV-seropositive individuals treated with HAART syngeneic cells from their HIV-seronegative identical twins followed by IL-2. Absolute and percent CD4 cell counts rose dramatically in vaccine recipients but not in control subjects treated with HAART only [89].…”

Section: Peripheral Blood-derived Live Vaccinesmentioning

confidence: 87%

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Therapeutic AIDS Vaccines

Bourinbaiar¹,

Root‐Bernstein²,

Abulafia-Lapid³

et al. 2006

CPD

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Therapeutic HIV vaccines represent promising strategy as an adjunct or alternative to current antiretroviral treatment options for HIV. Unlike prophylactic AIDS vaccines designed to prevent HIV infection, therapeutic vaccines are given to already infected individuals to help fight the disease by modulating their immune response. The first immunotherapeutic trial in AIDS patients was conducted in 1983. Since then several dozen conventional therapeutic vaccine trials have been carried out. Unfortunately, the results have consistently shown that while HIV-specific immune responses were evident as a result of vaccination, the clinical improvement has been seldom observed. The instances of the apparent clinical benefit were invariably associated with unconventional vaccines that acted in accord with the principles of alloimmunization and/or autologous vaccination. All such vaccines were derived from the blood of HIV carriers or a cell culture and thus they inherently contained allo- or self-antigens unrelated to HIV. This intriguing observation raises the issue whether this clinically successful approach has been unduly neglected. The current strategy biased toward vaccines, which have shown little evidence of clinical efficacy, needs to be diversified and supplemented with research on alternative vaccine approaches geared toward immune tolerance induction.

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Section: Peripheral Blood-derived Live Vaccinesmentioning

confidence: 87%

“…The immunotherapy by adoptive transfer of syngeneic lymphocytes was tested in HIV-negative and HIV-positive identical twins [88,89]. In one study, the noninfected twin was vaccinated with a recombinant vaccinia virus expressing the envelope glycoprotein of his brother's viruses followed by boost with gp160 [88].…”

Section: Peripheral Blood-derived Live Vaccinesmentioning

confidence: 99%

Therapeutic AIDS Vaccines

Bourinbaiar¹,

Root‐Bernstein²,

Abulafia-Lapid³

et al. 2006

CPD

View full text Add to dashboard Cite

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“…Secondly, in one pilot trial of ATT, HAART plus interleukin‐2 and adoptive cellular therapy using in vitro activated T‐cell lines was superior to HAART alone (Tsoukas et al , 2001). Another study on the adoptive transfer of autologous and co‐stimulated CD4 + T cells showed that the transfer induced the expansion of peripheral T cells (Levine et al , 2002).…”

Section: Discussionmentioning

confidence: 99%

“…This was a requirement for enrolment because several large studies had shown biphasic kinetics of CD4 + T cells with a rapid increase during the first 8-12 weeks on HAART, which is possibly due to cell redistribution from the lymphoid tissue (Pakker et al, 1998;Bucy et al, 1999). Secondly, in one pilot trial of ATT, HAART plus interleukin-2 and adoptive cellular therapy using in vitro activated T-cell lines was superior to HAART alone (Tsoukas et al, 2001). Another study on the adoptive transfer of autologous and co-stimulated CD4 + T cells showed that the transfer induced the expansion of peripheral T cells (Levine et al, 2002).…”

Section: Long-term Immunological Benefitmentioning

confidence: 99%

Adoptive transfer of syngeneic T cells in HIV‐1 discordant twins indicates rapid regulation of T‐cell homeostasis

et al. 2007

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Summary The safety and efficacy of adoptive T‐cell transfer (ATT) was tested in the context of viral suppression in syngeneic twins discordant for human immunodeficiency virus type 1 (HIV‐1) infection. Human leucocyte antigen‐matched T cells of seven HIV‐negative twins were obtained by lymphapheresis and immediately transfused into the HIV‐infected sibling. Four twins received 12 ATTs each, with a mean of 2·10 ± 0·97 × 109 CD4+ T cells and 1·74 ± 0·81 × 109 CD8+ T cells. Additional transfers were performed in three more twin pairs to study the short‐term kinetics of transfused syngeneic T cells. Mean CD4+ T‐cell counts increased significantly, by 0·133 ± 0·136 × 109 cells/l at 1 h and 0·144 ± 0·12 × 109 cells/l at 3 h post‐transfusion (P < 0·0001). Short‐term kinetic studies suggested a rapid clearance of transferred T cells from the peripheral blood within minutes due to a distribution to marginal pools. After a mean follow up of 39 months, however, a sustained increase of the mean CD4+ T‐cell count was observed (from 0·232 × 109 to 0·523 × 109 cells/l) without changes of plasma viraemia. We conclude that ATT combined with highly active antiretroviral therapy is safe and leads to a considerable increase in CD4+ T‐cell numbers. The clearance kinetics of the transfused cells from peripheral blood indicates a very rapid regulation of T‐cell homeostasis in HIV infection.

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“…In these patients, rhuIL-2 can augment immune responses and increase CD4+ T lymphocyte counts (Aladdin et al, 2000;Davey et al, 1997;Jacobson et al, 1996). Recombinant huIL-2 has also been administered to HIV-1-infected individuals to support adoptively transferred HIV-1-specific lymphocytes and CTL (Klimas et al, 1994;Koenig et al, 1995b;Tsoukas et al, 2001). In addition, low-dose aldesleukin, a modified form of rhuIL-2, has been used successfully to support adoptively transferred MART-1 specific CTL clones in metastatic melanoma patients (Yee et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Failure of low-dose recombinant human IL-2 to support the survival of virus-specific CTL clones infused into severe combined immunodeficient foals: Lack of correlation between in vitro activity and in vivo efficacy

Mealey

Littke

Leib

et al. 2008

Veterinary Immunology and Immunopathology

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Although CTL are important for control of lentiviruses, including equine infectious anemia virus (EIAV), it is not known if CTL can limit lentiviral replication in the absence of CD4 help and neutralizing antibody. Adoptive transfer of EIAV-specific CTL clones into severe combined immunodeficient (SCID) foals could resolve this issue, but it is not known whether exogenous IL-2 administration is sufficient to support the engraftment and proliferation of CTL clones infused into immunodeficient horses. To address this question we adoptively transferred EIAV Rev-specific CTL clones into four EIAV-challenged SCID foals, concurrent with low-dose aldesleukin (180,000 U/ m 2 ), a modified recombinant human IL-2 (rhuIL-2) product. The dose was calculated based on the specific activity on equine PBMC in vitro, and resulted in plasma concentrations considered sufficient to saturate high affinity IL-2 receptors in humans. Despite specific activity on equine PBMC that was equivalent to recombinant equine IL-2 and another form of rhuIL-2, aldesleukin did not support the engraftment and expansion of infused CTL clones, and control of viral load and clinical disease did not occur. It was concluded that survival of Rev-specific CTL clones infused into EIAVchallenged SCID foals was not enhanced by aldesleukin at the doses used in this study, and that in vitro specific activity did not correlate with in vivo efficacy. Successful adoptive immunotherapy with CTL clones in immunodeficient horses will likely require higher doses of rhuIL-2, co-infusion of CD4+ T lymphocytes, or administration of equine IL-2.

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Improvement of HIV-Specific Immunity in HIV-Infected Twins Treated with Highly Active Antiretroviral Therapy, Interleukin 2, and Syngeneic Adoptively Transferred Cells

Cited by 7 publications

References 55 publications

Therapeutic AIDS Vaccines

Therapeutic AIDS Vaccines

Adoptive transfer of syngeneic T cells in HIV‐1 discordant twins indicates rapid regulation of T‐cell homeostasis

Failure of low-dose recombinant human IL-2 to support the survival of virus-specific CTL clones infused into severe combined immunodeficient foals: Lack of correlation between in vitro activity and in vivo efficacy

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